Review Reports - The Interest in Nanomaterials for Topical Photoprotection

Round 1

Reviewer 1 Report

In the present manuscript, the authors Couteau and Coiffard present a kind of state of the art regarding the use and efficiency of UV-filters in sunscreen. A large panel of nano-TiO2 and nano-ZnO filters is presented as well as two organic filters. SPF values are measured for all the filters considered and briefly discussed.

My overall comment is that the data presented bring a lot of questions that are not addressed in the manuscript. Before publication in Cosmetics, I recommend the authors to consider and try to answer these questions below to give more novelty and utility to their work.

l. 32 : The trade name Tayca MT-100TV given in the abstract does not appear in the manuscript. It seems that the Eusolex TS gives the SPF close to 40 described here.

l. 136: “A certain number of incorporated ingredients enable the SPF to be artificially increased.”

This comment is only true with in vivo measured SPF. This limitation should be reminded in the sentence.

l.141: The Al coating is described here as preventing the nanoparticle agglomeration. Actually the first aim of this mineral layer (e.g. alumina and silica found in Table 1) is to stop the ROS generation by the photocatalytic TiO2 and to facilitate the covalent grafting of the organic outermost coating. The dispersion of the nanoparticles in the cream is rather favoured by this latter (stearic acid, simethicone…), giving most of the time a lipophilic character to the nanoparticles, i.e. affinity for the oil phase of the emulsion. On the other hand, the aluminium oxide layer does not bring any particular higher dispersion stability compared to TiO2 surface, as both of these metal oxides have a hydrophilic character and points of zero charge close to neutral pH.

This point should be clarified in the manuscript.

l. 142: “The raw materials which tend to slow down the appearance of sunburn without actually having a photo-protective effect per se are a danger for the consumer who is no longer warned by the appearance of sunburn.”

I would like the authors to clarify this sentence at this introductive point of the manuscript. How sunburn can be delayed if photoprotection is not efficient? The distinction made between both mechanisms should be mentioned here.

l. 147: Why is PMMA the easiest material to measure in vitro SPF? Does it mimic skin in term of roughness and affinity to the cream spreading? Is it transparent to UV?

Tables 3 and 4:

I think that one main missing TiO2 sample reference not considered in this work should be pure and nanometric rutile free of any coating. This reference could be more likely compared to the commercial UV filters studied here as they would be of similar size, surface area, number of particles... The comparison would inform on the effect of the coating on SPF. On an other hand such reference could be compared to the LCW standard Titanium Oxide studied here to inform on the role of the particle size. Otherwise, there are currently more than one parameter varying at a time in Table 3 making difficult to distinguish their respective effects.

Table 4:

The SPF values given in Table 4 are contrasted and call for a discussion currently not proposed in the manuscript. I would like the authors to discuss the following observations:

Eusolex TS has a SPF +11 compared to the Eusolex T-2000, while the only difference appearing between these filters is the nature of the organic coating (stearic acid vs. simethicone). Since the organic coating controls the filter dispersion in the emulsion, is there a better dispersion obtained with the stearic acid used in Eusolex TS, inducing the observed higher SPF?

Same kind of question regarding Eusolex T-Avo compared to UV Titan X-140. The former has no organic coating but only a silica layer on the TiO2, implying a hydrophilic character, and giving a SPF of 28. The latter has only Glycerin as an additional component and gives a lower SPF of 12. Where goes the glycerine? Is it responsible for such a decreased in SPF?

The hydrophilic filters certainly go to the water phase of the emulsion while the lipophilic ones go to the oil phase. They should be distinguished in Table 3. What is the consequence in term of SPF for the O/W cream used here. Can we conclude on a better UV filtration when the nanoparticles are in the dispersed phase?

Even if no evident conclusion can be given from the current set of data, I think that a discussion from the authors giving their opinions on these points would be very welcome.

10.

Table 3 and 4: The filter Parsol TX (DSM) presented in Table 3 is not given in Table 4 in term of SPF. Please complete or delete.

11.

l. 176: “It appears that uncoated pigmentary size titanium dioxide is only of minor interest in terms of topical photoprotection”

Why are micro-TiO2 less efficient UV filters than nano-TiO2 at a given concentration? This should be discussed here. I expect it is related to the better dispersion and higher particle number in the case of nanoparticles. Can we imagine that microparticles constitute local patch-like filters in the emulsion while nanoparticles are more homogenously dispersed?

12.

l.185-187:

The fear of consumers regarding organic filters may also be due to the known negative impact of those filters to the environment.

See e.g. Danovaro work: Danovaro R. et al., 2008. Sunscreens cause coral bleaching by promoting viral infections. Environmental Health Perspectives 116, 441-447.

13.

l. 193: “…, as organic SPPs only contain inorganic filters.”

I don’t understand this part of the sentence as SPPs do not contain only inorganic filters. Could it be developed?

14.

l.201:

Still on a psychological and marketing point of view, we could expect an opposite consumer thought: The cream that can not be seen by the naked eye is more frequently consumed (typically every hours on the beach) since the consumer wonders if the protective layer is still present on his skin. This in turn implies better and longer sun protection, in addition to higher aesthetic compatibility. It would be interesting to balance these two consumer reasonings to know which market is the most profitable, SPP efficiency put apart.

15.

l. 211:

I think this comment is only valid for SPF measured in vivo. It should be mentioned.

16.

l. 212:

It can not be said that only the nanoparticulate TiO2 is photocatalytic and micro-TiO2 is not. Both are actually photocacatlytic, but nano-TiO2 shows a greater photoreactivity than micro-TiO2, which is attributed predominantly to its larger surface area, reduced eCB−/hVB+ recombination and faster charge transfer.

See e.g.:

Influence of Titanium Dioxide Particle Size on the Photostability of the Chemical UV-Filters Butyl Methoxy Dibenzoylmethane and Octocrylene in a Microemulsion, by Jutta Kockler, Michael Oelgemöller, Sherryl Robertson and Beverley D. Glass, Cosmetics 2014, 1, 128-139; doi:10.3390/cosmetics1020128

Zhang, Z.B.; Wang, C.C.; Zakaria, R.; Ying, J.Y. Role of particle size in nanocrystalline

TiO2-based photocatalysts. J. Phys. Chem. B 1998, 102, 10871–10878

17.

l. 233: “Concerning the impact on the environment, … there is almost no data at the present time.”

I don’t agree. Even if more data is always needed, there has been actually a lot of studies devoted to the environmental impact of nanotechnologies. TiO2 nanoparticles are among the most studied nanomaterials since produced in highest quantities. A part of them is devoted to the UV filters used in sunscreen. They should be considered in the present manuscript.

See e.g. below:

1. Ahn, S., et al. 2008. Alternative evaluation method in vitro for the water-resistant effect of sunscreen products. Skin Res. Technol. 14 (2), 187-191.

2. Auffan, M., 2010 Structural degradation at the surface of a TiO(2)-based nanomaterial used in cosmetics. Environ. Sci. Technol. 44 (7), 2689-2694.

3. Danovaro, R., et al. 2008 Sunscreens cause coral bleaching by promoting viral infections. Environ. Health Perspect. 116 (4), 441-447.

4. Labille, J. et al.., 2010 Aging of TiO(2) nanocomposites used in sunscreen. Dispersion and fate of the degradation products in aqueous environment. Environ. Pollut. 158 (12), 3482-3489.

5. Langford, K.H., Thomas, K.V., 2008 Inputs of chemicals from recreational activities into the Norwegian coastal zone. J. Environ. Monit. 10 (7), 894-898.

6. Poiger, T. et al. 2004 Occurrence of UV filter compounds from sunscreens in surface waters: regional mass balance in two Swiss lakes. Chemosphere 55 (7), 951-963.

7. Botta C. et al. 2011 TiO2-based nanoparticles released in water from commercialized sunscreens in a life-cycle perspective: Structures and quantities. Environmental Pollution 159 (2011) 1543-1550

8. Sunscreens as a Source of Hydrogen Peroxide Production in Coastal Waters, By: Sanchez-Quiles et al. ENVIRONMENTAL SCIENCE & TECHNOLOGY Volume: 48 Issue: 16 Pages: 9037-9042

9. Release of TiO2 Nanoparticles from Sunscreens into Surface Waters: A One-Year Survey at the Old Danube Recreational Lake. By: Gondikas, A. et al. ENVIRONMENTAL SCIENCE & TECHNOLOGY Volume: 48 Issue: 10 Pages: 5415-5422, in 2014

10. Effects of aging on structure and stability of TiO2 nanoparticle-containing oil-in-water emulsions By: Rossano, M. et al. INTERNATIONAL JOURNAL OF PHARMACEUTICS Volume: 461 Issue: 1-2 Pages: 89-96 Published: JAN 30 2014

11. Aquatic toxicity of manufactured nanomaterials: challenges and recommendations for future toxicity testing By: Schultz, A. et al., ENVIRONMENTAL CHEMISTRY Volume: 11 Issue: 3 Pages: 207-226 Published: 2014

12. Sunscreen Products as Emerging Pollutants to Coastal Waters, By: Tovar-Sanchez, A. et al., PLOS ONE Volume: 8 Issue: 6 Article Number: e65451 Published: JUN 5 2013

13. Santaella C., et al. Aged TiO2-based nanocomposite used in sunscreens produces singlet oxygen under long-wave UV and sensitizes Escherichia coli to cadmium Environ. Sci. Technol. (2014) vol. 48 (9) 5245-5253

14. Fouqueray M., et al. Exposure of juvenile Danio rerio to aged TiO2 nanomaterial from sunscreen. Environ. Sci. Pollut. Res. (2013) vol. 20 (5) 3340-3350

15. Jomini S., et al. Modifications of the Bacterial Reverse Mutation Test Reveals Mutagenicity of TiO2 Nanoparticles and Byproducts from a Sunscreen TiO2-Based Nanocomposite. Toxicology Letters (2012) vol. 215 (1) 54-61

16. Fouqueray M., et al. Effect of aged TiO2 nanocomposite from sunscreen on Daphnia magna exposed by dietary route. Environmental Pollution (2012) vol. 163, 55-61.

17. Foltête A.S. et al. Environmental impact of sunscreen nanomaterials: ecotoxicity and genotoxicity of altered TiO2 nanocomposites on Vicia faba. Environmental Pollution (2011) vol. 159 (10) 2515-2522

18. Bigorgne E., et al. Ecotoxicological assessment of an altered TiO2 nanocomposite on the earthworm Eisenia fétida Environmental Pollution (2011) vol. 159 (10) 2698-2705

19. Lapied E. et al. Ecotoxicological effects of an aged TiO2 nanocomposite measured as apoptosis in the anecic earthworm Lumbricus terrestris after exposure through water, food and soil. Environment International (2011) vol. 37, p. 1105-1110

18.

How do the two organic filters tested here work? How do they stop UV rays?

These two filters are hydrophilic. Shall we expect a higher SPF if they were tested in a W/O emulsion? Why the authors selected these two filters among a huge list of existing organic filters?

19.

Conclusion:

The conclusion does not really consider the data presented in the manuscript, but rather goes on the discussion. I would like the authors to comment the SPF values obtained with the TiO2 filters compared to the organic filters. Should these two types put in opposition or should they be used together? Which one is the most efficient UV filter and why? Which one is the safest and why? These are open questions that the authors could contribute to partly answer in the conclusion.

Minor corrections

l. 80 : correct “…due to the fact that it is…”

l.165: Remove “and”, I think.

l. 175: replace ref 18 by 17 (Couteau 2008a)

l. 291: remove “with”.

l. 292: please introduce the p53 tumour-suppressor gene.

Author Response

Author Response File: Author Response.pdf

Reviewer 2 Report

In the manuscript “The Interest of Nanomaterials in Topical Photoprotection” the authors review the role of nanoparticles for photoprotection products. Overall the manuscript is well written and the content suitably chosen and presented exept for the figures.

Some sentences should be clarified and minor issues in the text addressed before publication. The style of all the figures is unsatisfactory and must be improved.

Detailed comments to the text:

1. Titel: The title should read: “The interest in Nanomaterials for Topical Photoprotection”

2. Line 28-29:”..enables it to be concluded..” should read “enables to conclude”

3. Line 30: “SPF” should be written out in the abstract

4. Line 89: “…depending to the supplier” should read “…depending on the supplier”

5. Line 135/136: The two sentences starting with “Although, it is not..“ and “A certain number..” should be combined in one sentence.

6. Table 3: “Standard titanium oxide” is listed in table 3 as “example of commercial forms of titanium dioxide nanoparticles”. Strictly speaking “Standard titanium oxide” is not a nanoparticle since the size is 200 nm.

7. Table 3: The acronyms “INCI Name” and “MA” should be explained.

8. Line 188: namely “17 estradiol”, there seems to be missing something behind the 17

9. Line 218, 221, 224: TiO2 should be written with subscript “2”

10. Line 259: there are also quite interesting optical ways to study possible ZnO nanoparticle in humans in vivo. Include the following reference as an example: Breunig at al, BioNanoScience, Volume 5, Issue 1, pp 42-47, 2015.

11. Line 272: “launched on the market should read “launched onto the market”

12. Figure 1 and Figure 2. The black lines do not go the 0 for 0 %(w/w). Why? In Fig 2 There is even a data point at 0 % (w/w) but non-zero PF-UVA. Seems unreasonable.

13. Line 291: delete repeated “with”

14. Figure 3: Line does not go to zero for zero dose. Also, line bends down with higher dose at “10”. The overall trend the line is indicating seems unreasonable.

15. Figure 3 labels of both axes are missing.

16. Figure 4 labels of both axes are missing

17. Style and layout of Fig 1, 2 and Fig 3, 4 are different. Should be “harmonized”.

18. Line 315: “held responsible..” for what? Is there something missing?

should read: “The interest in Nanomaterials for Topical Photoprotection”